Thrombus

Image by Andre E.X. Brown

Unprovoked venous thromboembolism (VTE) may increase the risk of permanent work-related disability, according to research published in the Journal of Thrombosis and Haemostasis.

Researchers evaluated data from more than 60,000 people and found that individuals with unprovoked VTE had a 52% higher risk of work-related disability than those without VTE.

However, there was no association between provoked VTE and work-related disability.

In addition, only deep vein thrombosis (DVT)—not pulmonary embolism (PE)—was significantly associated with an increased risk of work-related disability.

For this study, the researchers analyzed data from the Tromsø Study and the Nord-Trøndelag Health Study, which enrolled 66,005 subjects from 1994 to 1997. The subjects’ mean age at inclusion was 41.3 (range, 20-65), and about half (51.2%, n=33,901) were women.

The subjects were followed through 2008. During the follow-up period, 384 individuals had a first VTE, and 9862 received a disability pension due to work-related disability.

Compared to individuals without VTE, those who had a VTE were slightly older and had a higher body mass index. VTE patients were more likely to have a history of cancer and cardiovascular disease, and they were more likely to have paying jobs.

In addition, subjects with VTE were more likely to have work-related disability. The crude incidence rate of disability was 37.5 per 1000 person-years among VTE patients and 13.5 per 1000 person-years among subjects without VTE.

VTE patients who received disability pension were slightly older than those who did not, and a higher proportion of the VTEs were DVTs rather than PEs. Half of the VTEs were unprovoked.

Multivariable analysis suggested that subjects with unprovoked VTE had a 52% higher risk of work-related disability than individuals without VTE (hazard ratio [HR]=1.52). However, there was no association between provoked VTE and work-related disability (HR=0.83).

When the researchers analyzed DVT and PE separately, they found that subjects with DVT had an 80% higher risk of work-related disability than those without DVT (HR=1.80). Subjects with PE had a moderately increased risk of work-related disability that was not statistically significant (HR=1.28).

When the researchers adjusted for baseline characteristics other than self-rated health, the association between work-related disability and DVT remained strong (HR=1.66), and there was no association between work-related disability and PE (HR=1.06).

The researchers said this study is the first of its kind to document a relationship between VTE and subsequent work-related disability. And the findings suggest the economic burden of VTE goes beyond costs to the healthcare system. The loss of economic output from people who are unable to work due to VTE-related complications is also a substantial economic cost of VTE.

Thrombus

Image by Andre E.X. Brown

Unprovoked venous thromboembolism (VTE) may increase the risk of permanent work-related disability, according to research published in the Journal of Thrombosis and Haemostasis.

Researchers evaluated data from more than 60,000 people and found that individuals with unprovoked VTE had a 52% higher risk of work-related disability than those without VTE.

However, there was no association between provoked VTE and work-related disability.

In addition, only deep vein thrombosis (DVT)—not pulmonary embolism (PE)—was significantly associated with an increased risk of work-related disability.

For this study, the researchers analyzed data from the Tromsø Study and the Nord-Trøndelag Health Study, which enrolled 66,005 subjects from 1994 to 1997. The subjects’ mean age at inclusion was 41.3 (range, 20-65), and about half (51.2%, n=33,901) were women.

The subjects were followed through 2008. During the follow-up period, 384 individuals had a first VTE, and 9862 received a disability pension due to work-related disability.

Compared to individuals without VTE, those who had a VTE were slightly older and had a higher body mass index. VTE patients were more likely to have a history of cancer and cardiovascular disease, and they were more likely to have paying jobs.

In addition, subjects with VTE were more likely to have work-related disability. The crude incidence rate of disability was 37.5 per 1000 person-years among VTE patients and 13.5 per 1000 person-years among subjects without VTE.

VTE patients who received disability pension were slightly older than those who did not, and a higher proportion of the VTEs were DVTs rather than PEs. Half of the VTEs were unprovoked.

Multivariable analysis suggested that subjects with unprovoked VTE had a 52% higher risk of work-related disability than individuals without VTE (hazard ratio [HR]=1.52). However, there was no association between provoked VTE and work-related disability (HR=0.83).

When the researchers analyzed DVT and PE separately, they found that subjects with DVT had an 80% higher risk of work-related disability than those without DVT (HR=1.80). Subjects with PE had a moderately increased risk of work-related disability that was not statistically significant (HR=1.28).

When the researchers adjusted for baseline characteristics other than self-rated health, the association between work-related disability and DVT remained strong (HR=1.66), and there was no association between work-related disability and PE (HR=1.06).

The researchers said this study is the first of its kind to document a relationship between VTE and subsequent work-related disability. And the findings suggest the economic burden of VTE goes beyond costs to the healthcare system. The loss of economic output from people who are unable to work due to VTE-related complications is also a substantial economic cost of VTE.

Thrombus

Image by Andre E.X. Brown

Unprovoked venous thromboembolism (VTE) may increase the risk of permanent work-related disability, according to research published in the Journal of Thrombosis and Haemostasis.

Researchers evaluated data from more than 60,000 people and found that individuals with unprovoked VTE had a 52% higher risk of work-related disability than those without VTE.

However, there was no association between provoked VTE and work-related disability.

In addition, only deep vein thrombosis (DVT)—not pulmonary embolism (PE)—was significantly associated with an increased risk of work-related disability.

For this study, the researchers analyzed data from the Tromsø Study and the Nord-Trøndelag Health Study, which enrolled 66,005 subjects from 1994 to 1997. The subjects’ mean age at inclusion was 41.3 (range, 20-65), and about half (51.2%, n=33,901) were women.

The subjects were followed through 2008. During the follow-up period, 384 individuals had a first VTE, and 9862 received a disability pension due to work-related disability.

Compared to individuals without VTE, those who had a VTE were slightly older and had a higher body mass index. VTE patients were more likely to have a history of cancer and cardiovascular disease, and they were more likely to have paying jobs.

In addition, subjects with VTE were more likely to have work-related disability. The crude incidence rate of disability was 37.5 per 1000 person-years among VTE patients and 13.5 per 1000 person-years among subjects without VTE.

VTE patients who received disability pension were slightly older than those who did not, and a higher proportion of the VTEs were DVTs rather than PEs. Half of the VTEs were unprovoked.

Multivariable analysis suggested that subjects with unprovoked VTE had a 52% higher risk of work-related disability than individuals without VTE (hazard ratio [HR]=1.52). However, there was no association between provoked VTE and work-related disability (HR=0.83).

When the researchers analyzed DVT and PE separately, they found that subjects with DVT had an 80% higher risk of work-related disability than those without DVT (HR=1.80). Subjects with PE had a moderately increased risk of work-related disability that was not statistically significant (HR=1.28).

When the researchers adjusted for baseline characteristics other than self-rated health, the association between work-related disability and DVT remained strong (HR=1.66), and there was no association between work-related disability and PE (HR=1.06).

The researchers said this study is the first of its kind to document a relationship between VTE and subsequent work-related disability. And the findings suggest the economic burden of VTE goes beyond costs to the healthcare system. The loss of economic output from people who are unable to work due to VTE-related complications is also a substantial economic cost of VTE.

I’m not exactly a devout follower of women’s college basketball. But having grown up in Knoxville, it was hard not to follow the University of Tennessee Lady Volunteers (“Lady Vols”) and the career of their longtime head coach, Pat Summitt. Summitt recently died from a swift and severe form of early-onset Alzheimer’s disease. In the wake of her death, many have analyzed the impact of her career and the legacy she has left from her lifetime of relentless coaching and developing of athletes. She was an incredible leader who should make us all reflect on the impact we are making in the lives of our patients and their families, our peers, and the next generation of hospitalists.

Early Career

Pat Summitt was born Patricia Sue Head in 1952 in Clarksville, Tenn., the daughter of Richard and Hazel Albright Head and the fourth of five children. When she was in high school, her family moved to another town so she could play basketball (as her local town did not have a girl’s team). Summitt attended the University of Tennessee at the Martin campus and played for its first women’s basketball coach. Although each of Summitt’s three brothers had received an athletic scholarship, at the time there were no athletic scholarships for women, so her parents supported her way through college.1

After college, Summitt started as a graduate assistant at the University of Tennessee. At the start of the 1974 basketball season, the head coach suddenly quit, and she was named the new head coach at the age of 22. (This was before women’s college basketball was even an NCAA-sanctioned sport.) Legend has it she was paid $250 a month and the team had almost no budget. She reportedly washed all the uniforms herself (which were purchased the year before from the proceeds of a doughnut sale) and drove the team van.1

Barely older than most of the players on the team, she coached her first game in December against Mercer University and lost 84–83. From then on, she racked up an incredible number of wins. In her second season, Summitt coached the team to a 16–11 record while working on her master’s degree in physical education.1

By 1978, Summitt recorded her 100th win and coached the Lady Vols in their first Association for Intercollegiate Athletics for Women Final Four. She ended the decade by winning their first-ever Southeastern Conference tournament. A few years later, in 1984, she coached the U.S. women’s team to an Olympic gold medal, becoming the first U.S. Olympian to win a basketball medal and coach a medal-winning team. There were countless other career milestones: She coached the Lady Vols in 16 SEC regular-season championships and 16 SEC tournament titles. She also coached the Lady Vols in 18 NCAA Final Fours.

Legacy

Summitt’s career-win total still stands as the most among NCAA Division I basketball coaches (men or women). Overall, Summitt finished her career with a record of 1,098-208 and a .841 winning percentage.

At the end of her career, there were 78 people mentored directly by her who were coaching basketball or working in administrative positions associated with the sport. Tennessee Athletic Director Dave Hart summarized her legacy:

“Pat Summitt is … truly is a global icon who transcended sports and spent her entire life making a difference in other peoples’ lives. … She was a genuine, humble leader who focused on helping people achieve more than they thought they were capable of accomplishing. … Her legacy will live on through the countless people she touched throughout her career.”2

Every player coached by Summitt finished her undergraduate degree, often with considerable prodding directly from her.

“Across the board with her kids, she also prepared them for life after basketball,” basketball coach Bob Knight said. “Not many people have prepared their players that well for life.”2

You don’t have to be a women’s basketball fan to understand and respect the impact that Summitt had on the lives she touched. She didn’t just win a lot of games—she changed the game. Think about how you will be remembered in your career as a hospitalist. Will you be remembered as someone clocking in and clocking out, just getting by for a paycheck? Or will you be remembered and revered as a “Summitt,” someone who always gave it their all and coached others to their best?

Hospital medicine is still in its relative infancy as a specialty. We all have the potential to pave a positive future for thousands more to come behind us; we all have the potential to be a Summitt. TH

References

1. Gregory S. Q&A: Tennessee Coach Pat Summitt. Time website. Accessed August 7, 2016.

2. Pat Summitt, winningest coach in Division I history, dies at 64. ESPN website. Accessed August 7, 2016.

I’m not exactly a devout follower of women’s college basketball. But having grown up in Knoxville, it was hard not to follow the University of Tennessee Lady Volunteers (“Lady Vols”) and the career of their longtime head coach, Pat Summitt. Summitt recently died from a swift and severe form of early-onset Alzheimer’s disease. In the wake of her death, many have analyzed the impact of her career and the legacy she has left from her lifetime of relentless coaching and developing of athletes. She was an incredible leader who should make us all reflect on the impact we are making in the lives of our patients and their families, our peers, and the next generation of hospitalists.

Early Career

Pat Summitt was born Patricia Sue Head in 1952 in Clarksville, Tenn., the daughter of Richard and Hazel Albright Head and the fourth of five children. When she was in high school, her family moved to another town so she could play basketball (as her local town did not have a girl’s team). Summitt attended the University of Tennessee at the Martin campus and played for its first women’s basketball coach. Although each of Summitt’s three brothers had received an athletic scholarship, at the time there were no athletic scholarships for women, so her parents supported her way through college.1

After college, Summitt started as a graduate assistant at the University of Tennessee. At the start of the 1974 basketball season, the head coach suddenly quit, and she was named the new head coach at the age of 22. (This was before women’s college basketball was even an NCAA-sanctioned sport.) Legend has it she was paid $250 a month and the team had almost no budget. She reportedly washed all the uniforms herself (which were purchased the year before from the proceeds of a doughnut sale) and drove the team van.1

Barely older than most of the players on the team, she coached her first game in December against Mercer University and lost 84–83. From then on, she racked up an incredible number of wins. In her second season, Summitt coached the team to a 16–11 record while working on her master’s degree in physical education.1

By 1978, Summitt recorded her 100th win and coached the Lady Vols in their first Association for Intercollegiate Athletics for Women Final Four. She ended the decade by winning their first-ever Southeastern Conference tournament. A few years later, in 1984, she coached the U.S. women’s team to an Olympic gold medal, becoming the first U.S. Olympian to win a basketball medal and coach a medal-winning team. There were countless other career milestones: She coached the Lady Vols in 16 SEC regular-season championships and 16 SEC tournament titles. She also coached the Lady Vols in 18 NCAA Final Fours.

Legacy

Summitt’s career-win total still stands as the most among NCAA Division I basketball coaches (men or women). Overall, Summitt finished her career with a record of 1,098-208 and a .841 winning percentage.

At the end of her career, there were 78 people mentored directly by her who were coaching basketball or working in administrative positions associated with the sport. Tennessee Athletic Director Dave Hart summarized her legacy:

“Pat Summitt is … truly is a global icon who transcended sports and spent her entire life making a difference in other peoples’ lives. … She was a genuine, humble leader who focused on helping people achieve more than they thought they were capable of accomplishing. … Her legacy will live on through the countless people she touched throughout her career.”2

Every player coached by Summitt finished her undergraduate degree, often with considerable prodding directly from her.

“Across the board with her kids, she also prepared them for life after basketball,” basketball coach Bob Knight said. “Not many people have prepared their players that well for life.”2

You don’t have to be a women’s basketball fan to understand and respect the impact that Summitt had on the lives she touched. She didn’t just win a lot of games—she changed the game. Think about how you will be remembered in your career as a hospitalist. Will you be remembered as someone clocking in and clocking out, just getting by for a paycheck? Or will you be remembered and revered as a “Summitt,” someone who always gave it their all and coached others to their best?

Hospital medicine is still in its relative infancy as a specialty. We all have the potential to pave a positive future for thousands more to come behind us; we all have the potential to be a Summitt. TH

References

1. Gregory S. Q&A: Tennessee Coach Pat Summitt. Time website. Accessed August 7, 2016.

2. Pat Summitt, winningest coach in Division I history, dies at 64. ESPN website. Accessed August 7, 2016.

I’m not exactly a devout follower of women’s college basketball. But having grown up in Knoxville, it was hard not to follow the University of Tennessee Lady Volunteers (“Lady Vols”) and the career of their longtime head coach, Pat Summitt. Summitt recently died from a swift and severe form of early-onset Alzheimer’s disease. In the wake of her death, many have analyzed the impact of her career and the legacy she has left from her lifetime of relentless coaching and developing of athletes. She was an incredible leader who should make us all reflect on the impact we are making in the lives of our patients and their families, our peers, and the next generation of hospitalists.

Early Career

Pat Summitt was born Patricia Sue Head in 1952 in Clarksville, Tenn., the daughter of Richard and Hazel Albright Head and the fourth of five children. When she was in high school, her family moved to another town so she could play basketball (as her local town did not have a girl’s team). Summitt attended the University of Tennessee at the Martin campus and played for its first women’s basketball coach. Although each of Summitt’s three brothers had received an athletic scholarship, at the time there were no athletic scholarships for women, so her parents supported her way through college.1

After college, Summitt started as a graduate assistant at the University of Tennessee. At the start of the 1974 basketball season, the head coach suddenly quit, and she was named the new head coach at the age of 22. (This was before women’s college basketball was even an NCAA-sanctioned sport.) Legend has it she was paid $250 a month and the team had almost no budget. She reportedly washed all the uniforms herself (which were purchased the year before from the proceeds of a doughnut sale) and drove the team van.1

Barely older than most of the players on the team, she coached her first game in December against Mercer University and lost 84–83. From then on, she racked up an incredible number of wins. In her second season, Summitt coached the team to a 16–11 record while working on her master’s degree in physical education.1

By 1978, Summitt recorded her 100th win and coached the Lady Vols in their first Association for Intercollegiate Athletics for Women Final Four. She ended the decade by winning their first-ever Southeastern Conference tournament. A few years later, in 1984, she coached the U.S. women’s team to an Olympic gold medal, becoming the first U.S. Olympian to win a basketball medal and coach a medal-winning team. There were countless other career milestones: She coached the Lady Vols in 16 SEC regular-season championships and 16 SEC tournament titles. She also coached the Lady Vols in 18 NCAA Final Fours.

Legacy

Summitt’s career-win total still stands as the most among NCAA Division I basketball coaches (men or women). Overall, Summitt finished her career with a record of 1,098-208 and a .841 winning percentage.

At the end of her career, there were 78 people mentored directly by her who were coaching basketball or working in administrative positions associated with the sport. Tennessee Athletic Director Dave Hart summarized her legacy:

“Pat Summitt is … truly is a global icon who transcended sports and spent her entire life making a difference in other peoples’ lives. … She was a genuine, humble leader who focused on helping people achieve more than they thought they were capable of accomplishing. … Her legacy will live on through the countless people she touched throughout her career.”2

Every player coached by Summitt finished her undergraduate degree, often with considerable prodding directly from her.

“Across the board with her kids, she also prepared them for life after basketball,” basketball coach Bob Knight said. “Not many people have prepared their players that well for life.”2

You don’t have to be a women’s basketball fan to understand and respect the impact that Summitt had on the lives she touched. She didn’t just win a lot of games—she changed the game. Think about how you will be remembered in your career as a hospitalist. Will you be remembered as someone clocking in and clocking out, just getting by for a paycheck? Or will you be remembered and revered as a “Summitt,” someone who always gave it their all and coached others to their best?

Hospital medicine is still in its relative infancy as a specialty. We all have the potential to pave a positive future for thousands more to come behind us; we all have the potential to be a Summitt. TH

References

1. Gregory S. Q&A: Tennessee Coach Pat Summitt. Time website. Accessed August 7, 2016.

2. Pat Summitt, winningest coach in Division I history, dies at 64. ESPN website. Accessed August 7, 2016.

Lab mouse

Preclinical research has revealed a potential treatment strategy for dyskeratosis congenita (DC).

Researchers found that DC is characterized by reductions in telomerase, telomere length, and telomere capping, which reduces Wnt pathway activity, resulting in intestinal stem cell failure.

However, treatment with Wnt agonists restored the Wnt-telomere feedback loop and reversed gastrointestinal DC phenotypes in vitro and in vivo.

Christopher J. Lengner, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues reported these discoveries in Cell Stem Cell.

“Right now, the main therapy for [DC] patients is a bone marrow transplant,” Dr Lengner said. “That can address the bone marrow failure but doesn’t fix other problems associated with the disease, and especially not the risk of cancer. This work suggests a way to address the underlying cause of the disease.”

Earlier research with mouse models of DC suggested there might be a connection between the Wnt pathway and telomerase. And a recent study in DC patients’ cells revealed a decrease in activity in the Wnt pathway.

So Dr Lengner and his colleagues wanted to explore whether activating Wnt could reverse the effects of the disease. To do so, the team used induced pluripotent stem cells (iPSCs), the CRISPR/Cas9 gene-editing system, and directed differentiation.

The researchers generated iPSCs from DKC1-mutant fibroblasts and from wild-type cells. The team also used CRISPR to introduce a DKC1 mutation into healthy human iPSCs and to correct the disease-causing mutation in iPSCs generated from DC patient samples.

The researchers then grew organoids through directed differentiation. iPSCs were coaxed to form a human intestinal organoid, which naturally forms a tube-like structure, recapitulating the tubes of the human gastrointestinal system.

When the researchers observed the development of intestinal organoids, they found that, initially, the DC cells seemed to form normally.

The original DKC1-mutant cells and the cells that had the DKC1 mutation introduced by CRISPR appeared to follow a normal course of development for several days. But by 2 weeks, they lacked the tube-like structure seen in the healthy samples and the disease-corrected samples.

The DKC1-mutant cells also had shorter telomeres, with the intestinal organoids from DC patients having the shortest of any cell type.

“We could see, at the molecular level, that this is accompanied by a failure to activate specific intestinal stem cell gene programs—specifically, genes in the Wnt pathway,” Dr Lengner said.

The next logical step was to activate Wnt to see if these defects could be reversed. The researchers treated organoids derived from DC patient iPSCs with a compound called CHIR that stimulates the Wnt pathway.

This restored the formation of the tube-like structure as well as intestinal stem cell gene expression. The treatment also increased telomerase activity and telomere length in the cells with mutant DKC1.

To assess this treatment approach in a more clinically relevant model, the researchers transplanted the human intestinal organoids into mice.

Mice that received a transplant containing the DKC1 mutation and received treatment with lithium, a stimulator of the Wnt pathway, maintained their intestinal tissue structure and had high expression of Wnt target genes.

In effect, these mice resembled the mice that received a transplant of an organoid derived from a healthy patient.

The researchers said this study offers proof of principle that activating the Wnt pathway can reverse at least the gastrointestinal phenotypes associated with DC. Looking ahead, the team would like to try accomplishing the same feat in other tissue types affected by the disease.

Lab mouse

Preclinical research has revealed a potential treatment strategy for dyskeratosis congenita (DC).

Researchers found that DC is characterized by reductions in telomerase, telomere length, and telomere capping, which reduces Wnt pathway activity, resulting in intestinal stem cell failure.

However, treatment with Wnt agonists restored the Wnt-telomere feedback loop and reversed gastrointestinal DC phenotypes in vitro and in vivo.

Christopher J. Lengner, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues reported these discoveries in Cell Stem Cell.

“Right now, the main therapy for [DC] patients is a bone marrow transplant,” Dr Lengner said. “That can address the bone marrow failure but doesn’t fix other problems associated with the disease, and especially not the risk of cancer. This work suggests a way to address the underlying cause of the disease.”

Earlier research with mouse models of DC suggested there might be a connection between the Wnt pathway and telomerase. And a recent study in DC patients’ cells revealed a decrease in activity in the Wnt pathway.

So Dr Lengner and his colleagues wanted to explore whether activating Wnt could reverse the effects of the disease. To do so, the team used induced pluripotent stem cells (iPSCs), the CRISPR/Cas9 gene-editing system, and directed differentiation.

The researchers generated iPSCs from DKC1-mutant fibroblasts and from wild-type cells. The team also used CRISPR to introduce a DKC1 mutation into healthy human iPSCs and to correct the disease-causing mutation in iPSCs generated from DC patient samples.

The researchers then grew organoids through directed differentiation. iPSCs were coaxed to form a human intestinal organoid, which naturally forms a tube-like structure, recapitulating the tubes of the human gastrointestinal system.

When the researchers observed the development of intestinal organoids, they found that, initially, the DC cells seemed to form normally.

The original DKC1-mutant cells and the cells that had the DKC1 mutation introduced by CRISPR appeared to follow a normal course of development for several days. But by 2 weeks, they lacked the tube-like structure seen in the healthy samples and the disease-corrected samples.

The DKC1-mutant cells also had shorter telomeres, with the intestinal organoids from DC patients having the shortest of any cell type.

“We could see, at the molecular level, that this is accompanied by a failure to activate specific intestinal stem cell gene programs—specifically, genes in the Wnt pathway,” Dr Lengner said.

The next logical step was to activate Wnt to see if these defects could be reversed. The researchers treated organoids derived from DC patient iPSCs with a compound called CHIR that stimulates the Wnt pathway.

This restored the formation of the tube-like structure as well as intestinal stem cell gene expression. The treatment also increased telomerase activity and telomere length in the cells with mutant DKC1.

To assess this treatment approach in a more clinically relevant model, the researchers transplanted the human intestinal organoids into mice.

Mice that received a transplant containing the DKC1 mutation and received treatment with lithium, a stimulator of the Wnt pathway, maintained their intestinal tissue structure and had high expression of Wnt target genes.

In effect, these mice resembled the mice that received a transplant of an organoid derived from a healthy patient.

The researchers said this study offers proof of principle that activating the Wnt pathway can reverse at least the gastrointestinal phenotypes associated with DC. Looking ahead, the team would like to try accomplishing the same feat in other tissue types affected by the disease.

Lab mouse

Preclinical research has revealed a potential treatment strategy for dyskeratosis congenita (DC).

Researchers found that DC is characterized by reductions in telomerase, telomere length, and telomere capping, which reduces Wnt pathway activity, resulting in intestinal stem cell failure.

However, treatment with Wnt agonists restored the Wnt-telomere feedback loop and reversed gastrointestinal DC phenotypes in vitro and in vivo.

Christopher J. Lengner, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues reported these discoveries in Cell Stem Cell.

“Right now, the main therapy for [DC] patients is a bone marrow transplant,” Dr Lengner said. “That can address the bone marrow failure but doesn’t fix other problems associated with the disease, and especially not the risk of cancer. This work suggests a way to address the underlying cause of the disease.”

Earlier research with mouse models of DC suggested there might be a connection between the Wnt pathway and telomerase. And a recent study in DC patients’ cells revealed a decrease in activity in the Wnt pathway.

So Dr Lengner and his colleagues wanted to explore whether activating Wnt could reverse the effects of the disease. To do so, the team used induced pluripotent stem cells (iPSCs), the CRISPR/Cas9 gene-editing system, and directed differentiation.

The researchers generated iPSCs from DKC1-mutant fibroblasts and from wild-type cells. The team also used CRISPR to introduce a DKC1 mutation into healthy human iPSCs and to correct the disease-causing mutation in iPSCs generated from DC patient samples.

The researchers then grew organoids through directed differentiation. iPSCs were coaxed to form a human intestinal organoid, which naturally forms a tube-like structure, recapitulating the tubes of the human gastrointestinal system.

When the researchers observed the development of intestinal organoids, they found that, initially, the DC cells seemed to form normally.

The original DKC1-mutant cells and the cells that had the DKC1 mutation introduced by CRISPR appeared to follow a normal course of development for several days. But by 2 weeks, they lacked the tube-like structure seen in the healthy samples and the disease-corrected samples.

The DKC1-mutant cells also had shorter telomeres, with the intestinal organoids from DC patients having the shortest of any cell type.

“We could see, at the molecular level, that this is accompanied by a failure to activate specific intestinal stem cell gene programs—specifically, genes in the Wnt pathway,” Dr Lengner said.

The next logical step was to activate Wnt to see if these defects could be reversed. The researchers treated organoids derived from DC patient iPSCs with a compound called CHIR that stimulates the Wnt pathway.

This restored the formation of the tube-like structure as well as intestinal stem cell gene expression. The treatment also increased telomerase activity and telomere length in the cells with mutant DKC1.

To assess this treatment approach in a more clinically relevant model, the researchers transplanted the human intestinal organoids into mice.

Mice that received a transplant containing the DKC1 mutation and received treatment with lithium, a stimulator of the Wnt pathway, maintained their intestinal tissue structure and had high expression of Wnt target genes.

In effect, these mice resembled the mice that received a transplant of an organoid derived from a healthy patient.

The researchers said this study offers proof of principle that activating the Wnt pathway can reverse at least the gastrointestinal phenotypes associated with DC. Looking ahead, the team would like to try accomplishing the same feat in other tissue types affected by the disease.

A 33-year-old African-American man is referred to dermatology—somewhat reluctantly—by his primary care provider for evaluation. A “fungal infection” has affected his fingernail on and off for several years, persisting despite four months of terbinafine treatment (250 mg/d).

The patient denies any antecedent trauma to the finger. He does have a history of hand eczema, mostly affecting the palmar surface of his hand, and atopy, marked by seasonal allergies and sensitive skin.

EXAMINATION
The patient’s fourth fingernail on his right hand is significantly dystrophic, with transverse ridges and modest onychorrhexis. The cuticle is detached from the nail plate, but the distal nail plate appears normal.

There are signs of his dyshidrotic hand eczema, with several 2 to 3 mm intradermal vesicles in the distal palm. Some spill onto the sides of his fingers.

What is the diagnosis?

DISCUSSION
To the unwary provider, every fingernail problem is fungal in nature; they simply have no other items in their differential, which is why terbinafine is overprescribed for nonfungal conditions. Even when we suspect fungal infection, the appropriate course would be to sample the nail plate and send it for culture or pathologic examination—not just throw another prescription at it.

However, in cases such as this one, there are other explanations. This patient’s nail issues are secondary to his eczema and are likely related to the disconnect between the cuticle and the nail plate. This gap allows debris (bits of food, dirt, etc) access to the nail matrix, thereby causing a misshapen nail. The key to diagnosis is the transverse ridging and detached cuticles. A history of hand eczema bolsters this impression—infection is not involved.

Application of a mid-strength steroid ointment to the cuticle area encourages it to reattach to the nail. This gives the nail a chance to grow in normally.

TAKE-HOME LEARNING POINTS
• Fungal infections are significantly (18 times) more common on toenails than on fingernails.
• Eczema on the hand or body can also lead to transverse ridges in fingernails, especially when the cuticle detaches from the nail plate.
• Other items in the differential include psoriasis, lichen planus, and nail changes associated with alopecia areata.

A 33-year-old African-American man is referred to dermatology—somewhat reluctantly—by his primary care provider for evaluation. A “fungal infection” has affected his fingernail on and off for several years, persisting despite four months of terbinafine treatment (250 mg/d).

The patient denies any antecedent trauma to the finger. He does have a history of hand eczema, mostly affecting the palmar surface of his hand, and atopy, marked by seasonal allergies and sensitive skin.

EXAMINATION
The patient’s fourth fingernail on his right hand is significantly dystrophic, with transverse ridges and modest onychorrhexis. The cuticle is detached from the nail plate, but the distal nail plate appears normal.

There are signs of his dyshidrotic hand eczema, with several 2 to 3 mm intradermal vesicles in the distal palm. Some spill onto the sides of his fingers.

What is the diagnosis?

DISCUSSION
To the unwary provider, every fingernail problem is fungal in nature; they simply have no other items in their differential, which is why terbinafine is overprescribed for nonfungal conditions. Even when we suspect fungal infection, the appropriate course would be to sample the nail plate and send it for culture or pathologic examination—not just throw another prescription at it.

However, in cases such as this one, there are other explanations. This patient’s nail issues are secondary to his eczema and are likely related to the disconnect between the cuticle and the nail plate. This gap allows debris (bits of food, dirt, etc) access to the nail matrix, thereby causing a misshapen nail. The key to diagnosis is the transverse ridging and detached cuticles. A history of hand eczema bolsters this impression—infection is not involved.

Application of a mid-strength steroid ointment to the cuticle area encourages it to reattach to the nail. This gives the nail a chance to grow in normally.

TAKE-HOME LEARNING POINTS
• Fungal infections are significantly (18 times) more common on toenails than on fingernails.
• Eczema on the hand or body can also lead to transverse ridges in fingernails, especially when the cuticle detaches from the nail plate.
• Other items in the differential include psoriasis, lichen planus, and nail changes associated with alopecia areata.

A 33-year-old African-American man is referred to dermatology—somewhat reluctantly—by his primary care provider for evaluation. A “fungal infection” has affected his fingernail on and off for several years, persisting despite four months of terbinafine treatment (250 mg/d).

The patient denies any antecedent trauma to the finger. He does have a history of hand eczema, mostly affecting the palmar surface of his hand, and atopy, marked by seasonal allergies and sensitive skin.

EXAMINATION
The patient’s fourth fingernail on his right hand is significantly dystrophic, with transverse ridges and modest onychorrhexis. The cuticle is detached from the nail plate, but the distal nail plate appears normal.

There are signs of his dyshidrotic hand eczema, with several 2 to 3 mm intradermal vesicles in the distal palm. Some spill onto the sides of his fingers.

What is the diagnosis?

DISCUSSION
To the unwary provider, every fingernail problem is fungal in nature; they simply have no other items in their differential, which is why terbinafine is overprescribed for nonfungal conditions. Even when we suspect fungal infection, the appropriate course would be to sample the nail plate and send it for culture or pathologic examination—not just throw another prescription at it.

However, in cases such as this one, there are other explanations. This patient’s nail issues are secondary to his eczema and are likely related to the disconnect between the cuticle and the nail plate. This gap allows debris (bits of food, dirt, etc) access to the nail matrix, thereby causing a misshapen nail. The key to diagnosis is the transverse ridging and detached cuticles. A history of hand eczema bolsters this impression—infection is not involved.

Application of a mid-strength steroid ointment to the cuticle area encourages it to reattach to the nail. This gives the nail a chance to grow in normally.

TAKE-HOME LEARNING POINTS
• Fungal infections are significantly (18 times) more common on toenails than on fingernails.
• Eczema on the hand or body can also lead to transverse ridges in fingernails, especially when the cuticle detaches from the nail plate.
• Other items in the differential include psoriasis, lichen planus, and nail changes associated with alopecia areata.

All infants who either exhibit abnormal clinical or neuroimaging findings consistent with possible Zika infection, or who exhibit normal phenotypes but are born to mothers who are positive for Zika virus infection during pregnancy, should undergo laboratory testing for the virus, according to updated diagnostic guidance from the CDC.

All infants should undergo a comprehensive physical exam at birth, as well as a neurologic examination, postnatal head ultrasound, and standard hearing tests to determine any phenotypic signs of congenital Zika infections (MMWR. ePub: 2016 Aug 19. doi: 10.15585/mmwr.mm6533e2).

©Devonyu/Thinkstock

Laboratory samples should be collected within 2 days of birth. Molecular testing should be done via a real-time reverse transcription–polymerase chain reaction (rRT-PCR), while serologic testing should be carried out via IgM. If the former test is positive, then the infant is Zika positive; however, if the rRT-PCR is negative but the IgM is positive, then the conclusion can only be a “probable” congenital Zika infection.

For infants with laboratory-confirmed or probable congenital Zika infection, the CDC recommends outpatient management and follow-up. For those who are found negative for Zika despite having other symptoms consistent with infection, the CDC advises continued evaluation to determine the cause of any congenital anomalies.

If an infant has no overt symptoms of Zika virus but is found to have laboratory-confirmed or probable Zika, they should be given routine newborn care along with auditory brainstem response (ABR) testing and an opthalmology examination within 1 month of birth. Infants with no overt signs of Zika and a lab-confirmed negative result can resume standard newborn care with no additional monitoring.

Outpatient care should begin with clear establishment of a medical home, followed by monitoring the child’s growth and developmental screenings at every well child visit, according to the CDC. Vision screening should be repeated at all well child visits; ABR should be repeated 4-6 months after initial testing.

“Use a standardized, validated developmental screening tool at 9 months as currently recommended, or earlier for any parental or provider concerns,” according to lead author Kate Russell, MD, of the CDC’s Epidemic Intelligence Service, and her coauthors.

Cranial ultrasound should be performed on all infants, regardless of how normal any prenatal cranial ultrasounds were. Previously, the CDC advised that if a third trimester prenatal cranial ultrasound showed no abnormalities, a postnatal cranial ultrasound was not needed.

The CDC continues to advise that a multidisciplinary approach be taken to evaluation, diagnosis, and potential treatment of infants with congenital Zika virus infection.

“Because the types of services needed to care for infants with congenital Zika syndrome are complex, CDC recommends coordinated care through a multidisciplinary team and established medical home,” according to the guidance. “As a critical component of patient care and early identification of any delays, families should be empowered to be active participants in their child’s monitoring and care.”

[email protected]

All infants who either exhibit abnormal clinical or neuroimaging findings consistent with possible Zika infection, or who exhibit normal phenotypes but are born to mothers who are positive for Zika virus infection during pregnancy, should undergo laboratory testing for the virus, according to updated diagnostic guidance from the CDC.

All infants should undergo a comprehensive physical exam at birth, as well as a neurologic examination, postnatal head ultrasound, and standard hearing tests to determine any phenotypic signs of congenital Zika infections (MMWR. ePub: 2016 Aug 19. doi: 10.15585/mmwr.mm6533e2).

©Devonyu/Thinkstock

Laboratory samples should be collected within 2 days of birth. Molecular testing should be done via a real-time reverse transcription–polymerase chain reaction (rRT-PCR), while serologic testing should be carried out via IgM. If the former test is positive, then the infant is Zika positive; however, if the rRT-PCR is negative but the IgM is positive, then the conclusion can only be a “probable” congenital Zika infection.

For infants with laboratory-confirmed or probable congenital Zika infection, the CDC recommends outpatient management and follow-up. For those who are found negative for Zika despite having other symptoms consistent with infection, the CDC advises continued evaluation to determine the cause of any congenital anomalies.

If an infant has no overt symptoms of Zika virus but is found to have laboratory-confirmed or probable Zika, they should be given routine newborn care along with auditory brainstem response (ABR) testing and an opthalmology examination within 1 month of birth. Infants with no overt signs of Zika and a lab-confirmed negative result can resume standard newborn care with no additional monitoring.

Outpatient care should begin with clear establishment of a medical home, followed by monitoring the child’s growth and developmental screenings at every well child visit, according to the CDC. Vision screening should be repeated at all well child visits; ABR should be repeated 4-6 months after initial testing.

“Use a standardized, validated developmental screening tool at 9 months as currently recommended, or earlier for any parental or provider concerns,” according to lead author Kate Russell, MD, of the CDC’s Epidemic Intelligence Service, and her coauthors.

Cranial ultrasound should be performed on all infants, regardless of how normal any prenatal cranial ultrasounds were. Previously, the CDC advised that if a third trimester prenatal cranial ultrasound showed no abnormalities, a postnatal cranial ultrasound was not needed.

The CDC continues to advise that a multidisciplinary approach be taken to evaluation, diagnosis, and potential treatment of infants with congenital Zika virus infection.

“Because the types of services needed to care for infants with congenital Zika syndrome are complex, CDC recommends coordinated care through a multidisciplinary team and established medical home,” according to the guidance. “As a critical component of patient care and early identification of any delays, families should be empowered to be active participants in their child’s monitoring and care.”

[email protected]

All infants who either exhibit abnormal clinical or neuroimaging findings consistent with possible Zika infection, or who exhibit normal phenotypes but are born to mothers who are positive for Zika virus infection during pregnancy, should undergo laboratory testing for the virus, according to updated diagnostic guidance from the CDC.

All infants should undergo a comprehensive physical exam at birth, as well as a neurologic examination, postnatal head ultrasound, and standard hearing tests to determine any phenotypic signs of congenital Zika infections (MMWR. ePub: 2016 Aug 19. doi: 10.15585/mmwr.mm6533e2).

©Devonyu/Thinkstock

Laboratory samples should be collected within 2 days of birth. Molecular testing should be done via a real-time reverse transcription–polymerase chain reaction (rRT-PCR), while serologic testing should be carried out via IgM. If the former test is positive, then the infant is Zika positive; however, if the rRT-PCR is negative but the IgM is positive, then the conclusion can only be a “probable” congenital Zika infection.

For infants with laboratory-confirmed or probable congenital Zika infection, the CDC recommends outpatient management and follow-up. For those who are found negative for Zika despite having other symptoms consistent with infection, the CDC advises continued evaluation to determine the cause of any congenital anomalies.

If an infant has no overt symptoms of Zika virus but is found to have laboratory-confirmed or probable Zika, they should be given routine newborn care along with auditory brainstem response (ABR) testing and an opthalmology examination within 1 month of birth. Infants with no overt signs of Zika and a lab-confirmed negative result can resume standard newborn care with no additional monitoring.

Outpatient care should begin with clear establishment of a medical home, followed by monitoring the child’s growth and developmental screenings at every well child visit, according to the CDC. Vision screening should be repeated at all well child visits; ABR should be repeated 4-6 months after initial testing.

“Use a standardized, validated developmental screening tool at 9 months as currently recommended, or earlier for any parental or provider concerns,” according to lead author Kate Russell, MD, of the CDC’s Epidemic Intelligence Service, and her coauthors.

Cranial ultrasound should be performed on all infants, regardless of how normal any prenatal cranial ultrasounds were. Previously, the CDC advised that if a third trimester prenatal cranial ultrasound showed no abnormalities, a postnatal cranial ultrasound was not needed.

The CDC continues to advise that a multidisciplinary approach be taken to evaluation, diagnosis, and potential treatment of infants with congenital Zika virus infection.

“Because the types of services needed to care for infants with congenital Zika syndrome are complex, CDC recommends coordinated care through a multidisciplinary team and established medical home,” according to the guidance. “As a critical component of patient care and early identification of any delays, families should be empowered to be active participants in their child’s monitoring and care.”

[email protected]

About 10,000 newborns receive general anesthesia for congenital heart defects every year, and the more exposure they have to inhaled anesthetic agents, the greater effect it may have on their neurologic development, investigators at Children’s Hospital of Philadelphia reported in a study of newborns with hypoplastic left heart syndrome.

While previous studies have linked worse neurodevelopment to patient factors like prematurity and genetics, this is the first study to show a consistent relationship between neurodevelopment outcomes and modifiable factors during cardiac surgery in infants, Laura K. Diaz, MD, and her colleagues reported in the August issue of the Journal of Thoracic and Cardiovascular Surgery (J Thorac Cardiovasc Surg. 2016;152:482-9).

They studied 96 patients with hypoplastic left heart syndrome (HLHS) or similar syndromes who received volatile anesthetic agents (VAA) at their institution from 1998 to 2003. The patients underwent a battery of neurodevelopmental tests between the ages of 4 and 5 years that included full-scale IQ (FSIQ), verbal IQ (VIQ), performance IQ (PIQ), and processing speed.

“This study provides evidence that in children undergoing staged reconstructive surgery for HLHS, increasing cumulative exposure to VAAs beginning in infancy is associated with worse performance for FSIQ and VIQ, suggesting that VAA exposure may be a modifiable risk factor for adverse neurodevelopment outcomes,” Dr. Diaz and her colleagues wrote.

While survival has improved significantly in recent years for infants with hypoplastic left heart syndrome, physicians have harbored concerns that these children encounter neurodevelopmental issues later on. Dr. Diaz and her colleagues acknowledged that previous studies have shown factors, such as the use of cardiopulmonary bypass (CPB) and hospital length of stay, that could affect neurodevelopment in these children, but the findings have been inconsistent. Instead, those studies have shown such patient-specific factors as birth weight, ethnicity, and hereditary disorders were strong determinants of neurodevelopment in infants who have cardiac surgery, Dr. Diaz and her coauthors pointed out.

Their own previous study of patients with single-ventricle congenital heart disease concurred with the findings of those other studies, but it did not evaluate exposure to anesthesia (J. Thorac. Cardiovasc. Surg. 2014;147:1276-82). That was the focus of their current study.

Among the study group, 94 patients had an initial operation with CPB in their first 30 days of life. All 96 infants in the study group had additional operations, whether cardiac or noncardiac. The study tracked all anesthetic exposures up until the neurodevelopment evaluation in February 2008. All but 2 patients had initial VAA exposure at less than 1 year of age, and 45 at less than 1 month of age. Deep hypothermic circulatory arrest was used uniformly for aortic arch reconstruction.

The study used four different generalized linear models to evaluate anesthesia exposure and neurodevelopment.

For both FSIQ and PIQ, total minimum alveolar concentration hours were deemed to be statistically significant factors for lower scores. For PIQ, birth weight and length of postoperative hospital stay were statistically significant. For processing speed, gestational age and length of hospital stay were statistically significant.

Dr. Diaz and her colleagues said their findings are preliminary and do not justify a change in practice. “Prospective randomized, controlled multicenter clinical trials are indicated to continue to clarify the effects of early and repetitive exposure to VAA in this and other pediatric populations,” the study authors concluded.

Dr. Diaz and the study authors had no financial relationships to disclose.

About 10,000 newborns receive general anesthesia for congenital heart defects every year, and the more exposure they have to inhaled anesthetic agents, the greater effect it may have on their neurologic development, investigators at Children’s Hospital of Philadelphia reported in a study of newborns with hypoplastic left heart syndrome.

While previous studies have linked worse neurodevelopment to patient factors like prematurity and genetics, this is the first study to show a consistent relationship between neurodevelopment outcomes and modifiable factors during cardiac surgery in infants, Laura K. Diaz, MD, and her colleagues reported in the August issue of the Journal of Thoracic and Cardiovascular Surgery (J Thorac Cardiovasc Surg. 2016;152:482-9).

They studied 96 patients with hypoplastic left heart syndrome (HLHS) or similar syndromes who received volatile anesthetic agents (VAA) at their institution from 1998 to 2003. The patients underwent a battery of neurodevelopmental tests between the ages of 4 and 5 years that included full-scale IQ (FSIQ), verbal IQ (VIQ), performance IQ (PIQ), and processing speed.

“This study provides evidence that in children undergoing staged reconstructive surgery for HLHS, increasing cumulative exposure to VAAs beginning in infancy is associated with worse performance for FSIQ and VIQ, suggesting that VAA exposure may be a modifiable risk factor for adverse neurodevelopment outcomes,” Dr. Diaz and her colleagues wrote.

While survival has improved significantly in recent years for infants with hypoplastic left heart syndrome, physicians have harbored concerns that these children encounter neurodevelopmental issues later on. Dr. Diaz and her colleagues acknowledged that previous studies have shown factors, such as the use of cardiopulmonary bypass (CPB) and hospital length of stay, that could affect neurodevelopment in these children, but the findings have been inconsistent. Instead, those studies have shown such patient-specific factors as birth weight, ethnicity, and hereditary disorders were strong determinants of neurodevelopment in infants who have cardiac surgery, Dr. Diaz and her coauthors pointed out.

Their own previous study of patients with single-ventricle congenital heart disease concurred with the findings of those other studies, but it did not evaluate exposure to anesthesia (J. Thorac. Cardiovasc. Surg. 2014;147:1276-82). That was the focus of their current study.

Among the study group, 94 patients had an initial operation with CPB in their first 30 days of life. All 96 infants in the study group had additional operations, whether cardiac or noncardiac. The study tracked all anesthetic exposures up until the neurodevelopment evaluation in February 2008. All but 2 patients had initial VAA exposure at less than 1 year of age, and 45 at less than 1 month of age. Deep hypothermic circulatory arrest was used uniformly for aortic arch reconstruction.

The study used four different generalized linear models to evaluate anesthesia exposure and neurodevelopment.

For both FSIQ and PIQ, total minimum alveolar concentration hours were deemed to be statistically significant factors for lower scores. For PIQ, birth weight and length of postoperative hospital stay were statistically significant. For processing speed, gestational age and length of hospital stay were statistically significant.

Dr. Diaz and her colleagues said their findings are preliminary and do not justify a change in practice. “Prospective randomized, controlled multicenter clinical trials are indicated to continue to clarify the effects of early and repetitive exposure to VAA in this and other pediatric populations,” the study authors concluded.

Dr. Diaz and the study authors had no financial relationships to disclose.

About 10,000 newborns receive general anesthesia for congenital heart defects every year, and the more exposure they have to inhaled anesthetic agents, the greater effect it may have on their neurologic development, investigators at Children’s Hospital of Philadelphia reported in a study of newborns with hypoplastic left heart syndrome.

While previous studies have linked worse neurodevelopment to patient factors like prematurity and genetics, this is the first study to show a consistent relationship between neurodevelopment outcomes and modifiable factors during cardiac surgery in infants, Laura K. Diaz, MD, and her colleagues reported in the August issue of the Journal of Thoracic and Cardiovascular Surgery (J Thorac Cardiovasc Surg. 2016;152:482-9).

They studied 96 patients with hypoplastic left heart syndrome (HLHS) or similar syndromes who received volatile anesthetic agents (VAA) at their institution from 1998 to 2003. The patients underwent a battery of neurodevelopmental tests between the ages of 4 and 5 years that included full-scale IQ (FSIQ), verbal IQ (VIQ), performance IQ (PIQ), and processing speed.

“This study provides evidence that in children undergoing staged reconstructive surgery for HLHS, increasing cumulative exposure to VAAs beginning in infancy is associated with worse performance for FSIQ and VIQ, suggesting that VAA exposure may be a modifiable risk factor for adverse neurodevelopment outcomes,” Dr. Diaz and her colleagues wrote.

While survival has improved significantly in recent years for infants with hypoplastic left heart syndrome, physicians have harbored concerns that these children encounter neurodevelopmental issues later on. Dr. Diaz and her colleagues acknowledged that previous studies have shown factors, such as the use of cardiopulmonary bypass (CPB) and hospital length of stay, that could affect neurodevelopment in these children, but the findings have been inconsistent. Instead, those studies have shown such patient-specific factors as birth weight, ethnicity, and hereditary disorders were strong determinants of neurodevelopment in infants who have cardiac surgery, Dr. Diaz and her coauthors pointed out.

Their own previous study of patients with single-ventricle congenital heart disease concurred with the findings of those other studies, but it did not evaluate exposure to anesthesia (J. Thorac. Cardiovasc. Surg. 2014;147:1276-82). That was the focus of their current study.

Among the study group, 94 patients had an initial operation with CPB in their first 30 days of life. All 96 infants in the study group had additional operations, whether cardiac or noncardiac. The study tracked all anesthetic exposures up until the neurodevelopment evaluation in February 2008. All but 2 patients had initial VAA exposure at less than 1 year of age, and 45 at less than 1 month of age. Deep hypothermic circulatory arrest was used uniformly for aortic arch reconstruction.

The study used four different generalized linear models to evaluate anesthesia exposure and neurodevelopment.

For both FSIQ and PIQ, total minimum alveolar concentration hours were deemed to be statistically significant factors for lower scores. For PIQ, birth weight and length of postoperative hospital stay were statistically significant. For processing speed, gestational age and length of hospital stay were statistically significant.

Dr. Diaz and her colleagues said their findings are preliminary and do not justify a change in practice. “Prospective randomized, controlled multicenter clinical trials are indicated to continue to clarify the effects of early and repetitive exposure to VAA in this and other pediatric populations,” the study authors concluded.

Dr. Diaz and the study authors had no financial relationships to disclose.

A new appellate ruling protects doctors from federal prosecution when they recommend medical marijuana in accordance with state law.

In an Aug. 16 opinion, the 9th U.S. Circuit Court of Appeals ruled that the U.S. Department of Justice cannot spend funding to prosecute physicians and patients who allegedly violate federal drug laws if their actions comply with state medical cannabis statutes.

Smithore

The decision supports the longstanding policies of several medical specialty societies.

“The conflict between state and federal law regarding medical marijuana can be concerning for patients and physicians who may consider using or recommending marijuana as a treatment option,” Hilary Daniel, senior health policy analyst for the American College of Physicians, said in an interview. “We are encouraged that the decision by the 9th U.S. Circuit Court of Appeals may help to address some of these conflicts and remain cognizant of the potential challenges faced by physicians and patients outside the jurisdiction of the 9th Circuit.”

The ruling stems from a 2014 federal appropriations law that banned the Justice Department from interfering with state implementation of marijuana laws. Short-term measures since then have extended the prohibition, which now continues through Sept. 30, 2016. Defendants in 10 criminal cases sued the federal government, requesting their prosecutions be dismissed on the grounds that the Justice Department is prevented from spending funds to prosecute them. The parties were accused of various federal marijuana offenses, including conspiracy to manufacture and possession with intent to distribute. The Justice Department argued it is not preventing states from operating their medical marijuana laws by prosecuting private individuals. Three district courts declined to halt the prosecutions from proceeding.

But the appeals court ruled that the Justice Department is prohibited from spending funds from relevant federal appropriation to prosecute the defendants if their conduct was permitted by state medical marijuana laws. Judges remanded the cases to the district courts with instructions that if the Justice Department wishes to continue the cases, the appellants are entitled to hearings to determine whether their actions were authorized by state laws.

The decision is significant because it establishes an appellate level precedent regarding enforcement of the Congressional budget requirements, said Joshua Prober, general counsel and senior vice president for the American Osteopathic Association. However, the decision does not overturn federal criminal laws regarding marijuana use and is limited to the impact of Congress’ specific budgetary authorization measure, he said.

“As noted in the court’s opinion, it is quite possible that a future Congress will not put the same restrictions in place on federal prosecutorial activity,” Mr. Prober said in an interview. “And obviously there are the procedural limitations, i.e., the decision is only the view of one appellate circuit. It is possible that a different appellate court might find the Department of Justice’s arguments to be more persuasive.”

The appeals ruling comes less than a week after the U.S. Drug Enforcement Agency refused to reclassify marijuana under the Controlled Substances Act. Marijuana remains a schedule I controlled substance, noting in its decision that marijuana does not meet the criteria for currently accepted medical use in the United States, that there is a lack of accepted safety for its use under medical supervision, and that it has a high potential for abuse.

“The DEA and FDA continue to believe that scientifically valid and well-controlled clinical trials conducted under investigational new drug applications are the proper way to research all potential new medicines, including marijuana,” DEA Acting Administrator Chuck Rosenberg wrote in a letter to state governors. “Furthermore, we believe that the drug approval process is the proper way to assess whether a product derived from marijuana or its constituent parts is safe and effective for medical use.”

While tension between state and federal law regarding marijuana lingers, more states continue to approve marijuana for recreational and medical use, noted John A. DiNome, a health law attorney based in Philadelphia. So far, Oregon, Colorado, Washington, and Alaska allow recreational marijuana use, while 25 states have approved marijuana for medical use. At least 9 more states will consider recreational marijuana use in November.

“For the time being, the problem still exists,” Mr. DiNome said in an interview. “This temporarily keeps doctors off the hook from prosecution, but it doesn’t solve the underlying problem, which is: Is federal law going to change?”

[email protected]

On Twitter @legal_med

A new appellate ruling protects doctors from federal prosecution when they recommend medical marijuana in accordance with state law.

In an Aug. 16 opinion, the 9th U.S. Circuit Court of Appeals ruled that the U.S. Department of Justice cannot spend funding to prosecute physicians and patients who allegedly violate federal drug laws if their actions comply with state medical cannabis statutes.

Smithore

The decision supports the longstanding policies of several medical specialty societies.

“The conflict between state and federal law regarding medical marijuana can be concerning for patients and physicians who may consider using or recommending marijuana as a treatment option,” Hilary Daniel, senior health policy analyst for the American College of Physicians, said in an interview. “We are encouraged that the decision by the 9th U.S. Circuit Court of Appeals may help to address some of these conflicts and remain cognizant of the potential challenges faced by physicians and patients outside the jurisdiction of the 9th Circuit.”

The ruling stems from a 2014 federal appropriations law that banned the Justice Department from interfering with state implementation of marijuana laws. Short-term measures since then have extended the prohibition, which now continues through Sept. 30, 2016. Defendants in 10 criminal cases sued the federal government, requesting their prosecutions be dismissed on the grounds that the Justice Department is prevented from spending funds to prosecute them. The parties were accused of various federal marijuana offenses, including conspiracy to manufacture and possession with intent to distribute. The Justice Department argued it is not preventing states from operating their medical marijuana laws by prosecuting private individuals. Three district courts declined to halt the prosecutions from proceeding.

But the appeals court ruled that the Justice Department is prohibited from spending funds from relevant federal appropriation to prosecute the defendants if their conduct was permitted by state medical marijuana laws. Judges remanded the cases to the district courts with instructions that if the Justice Department wishes to continue the cases, the appellants are entitled to hearings to determine whether their actions were authorized by state laws.

The decision is significant because it establishes an appellate level precedent regarding enforcement of the Congressional budget requirements, said Joshua Prober, general counsel and senior vice president for the American Osteopathic Association. However, the decision does not overturn federal criminal laws regarding marijuana use and is limited to the impact of Congress’ specific budgetary authorization measure, he said.

“As noted in the court’s opinion, it is quite possible that a future Congress will not put the same restrictions in place on federal prosecutorial activity,” Mr. Prober said in an interview. “And obviously there are the procedural limitations, i.e., the decision is only the view of one appellate circuit. It is possible that a different appellate court might find the Department of Justice’s arguments to be more persuasive.”

The appeals ruling comes less than a week after the U.S. Drug Enforcement Agency refused to reclassify marijuana under the Controlled Substances Act. Marijuana remains a schedule I controlled substance, noting in its decision that marijuana does not meet the criteria for currently accepted medical use in the United States, that there is a lack of accepted safety for its use under medical supervision, and that it has a high potential for abuse.

“The DEA and FDA continue to believe that scientifically valid and well-controlled clinical trials conducted under investigational new drug applications are the proper way to research all potential new medicines, including marijuana,” DEA Acting Administrator Chuck Rosenberg wrote in a letter to state governors. “Furthermore, we believe that the drug approval process is the proper way to assess whether a product derived from marijuana or its constituent parts is safe and effective for medical use.”

While tension between state and federal law regarding marijuana lingers, more states continue to approve marijuana for recreational and medical use, noted John A. DiNome, a health law attorney based in Philadelphia. So far, Oregon, Colorado, Washington, and Alaska allow recreational marijuana use, while 25 states have approved marijuana for medical use. At least 9 more states will consider recreational marijuana use in November.

“For the time being, the problem still exists,” Mr. DiNome said in an interview. “This temporarily keeps doctors off the hook from prosecution, but it doesn’t solve the underlying problem, which is: Is federal law going to change?”

[email protected]

On Twitter @legal_med

A new appellate ruling protects doctors from federal prosecution when they recommend medical marijuana in accordance with state law.

In an Aug. 16 opinion, the 9th U.S. Circuit Court of Appeals ruled that the U.S. Department of Justice cannot spend funding to prosecute physicians and patients who allegedly violate federal drug laws if their actions comply with state medical cannabis statutes.

Smithore

The decision supports the longstanding policies of several medical specialty societies.

“The conflict between state and federal law regarding medical marijuana can be concerning for patients and physicians who may consider using or recommending marijuana as a treatment option,” Hilary Daniel, senior health policy analyst for the American College of Physicians, said in an interview. “We are encouraged that the decision by the 9th U.S. Circuit Court of Appeals may help to address some of these conflicts and remain cognizant of the potential challenges faced by physicians and patients outside the jurisdiction of the 9th Circuit.”

The ruling stems from a 2014 federal appropriations law that banned the Justice Department from interfering with state implementation of marijuana laws. Short-term measures since then have extended the prohibition, which now continues through Sept. 30, 2016. Defendants in 10 criminal cases sued the federal government, requesting their prosecutions be dismissed on the grounds that the Justice Department is prevented from spending funds to prosecute them. The parties were accused of various federal marijuana offenses, including conspiracy to manufacture and possession with intent to distribute. The Justice Department argued it is not preventing states from operating their medical marijuana laws by prosecuting private individuals. Three district courts declined to halt the prosecutions from proceeding.

But the appeals court ruled that the Justice Department is prohibited from spending funds from relevant federal appropriation to prosecute the defendants if their conduct was permitted by state medical marijuana laws. Judges remanded the cases to the district courts with instructions that if the Justice Department wishes to continue the cases, the appellants are entitled to hearings to determine whether their actions were authorized by state laws.

The decision is significant because it establishes an appellate level precedent regarding enforcement of the Congressional budget requirements, said Joshua Prober, general counsel and senior vice president for the American Osteopathic Association. However, the decision does not overturn federal criminal laws regarding marijuana use and is limited to the impact of Congress’ specific budgetary authorization measure, he said.

“As noted in the court’s opinion, it is quite possible that a future Congress will not put the same restrictions in place on federal prosecutorial activity,” Mr. Prober said in an interview. “And obviously there are the procedural limitations, i.e., the decision is only the view of one appellate circuit. It is possible that a different appellate court might find the Department of Justice’s arguments to be more persuasive.”

The appeals ruling comes less than a week after the U.S. Drug Enforcement Agency refused to reclassify marijuana under the Controlled Substances Act. Marijuana remains a schedule I controlled substance, noting in its decision that marijuana does not meet the criteria for currently accepted medical use in the United States, that there is a lack of accepted safety for its use under medical supervision, and that it has a high potential for abuse.

“The DEA and FDA continue to believe that scientifically valid and well-controlled clinical trials conducted under investigational new drug applications are the proper way to research all potential new medicines, including marijuana,” DEA Acting Administrator Chuck Rosenberg wrote in a letter to state governors. “Furthermore, we believe that the drug approval process is the proper way to assess whether a product derived from marijuana or its constituent parts is safe and effective for medical use.”

While tension between state and federal law regarding marijuana lingers, more states continue to approve marijuana for recreational and medical use, noted John A. DiNome, a health law attorney based in Philadelphia. So far, Oregon, Colorado, Washington, and Alaska allow recreational marijuana use, while 25 states have approved marijuana for medical use. At least 9 more states will consider recreational marijuana use in November.

“For the time being, the problem still exists,” Mr. DiNome said in an interview. “This temporarily keeps doctors off the hook from prosecution, but it doesn’t solve the underlying problem, which is: Is federal law going to change?”

[email protected]

On Twitter @legal_med

Dr. Scott Krugman, Chair of Pediatrics and Director of Medical Education at MedStar Franklin Square Medical Center in Baltimore, and Dr. Miguel Villagra, Medical Director of the Hospitalist Department at White River Medical Center in Batesville, AR talk about how residents and early career MDs process that decision.

Dr. Scott Krugman, Chair of Pediatrics and Director of Medical Education at MedStar Franklin Square Medical Center in Baltimore, and Dr. Miguel Villagra, Medical Director of the Hospitalist Department at White River Medical Center in Batesville, AR talk about how residents and early career MDs process that decision.

Dr. Scott Krugman, Chair of Pediatrics and Director of Medical Education at MedStar Franklin Square Medical Center in Baltimore, and Dr. Miguel Villagra, Medical Director of the Hospitalist Department at White River Medical Center in Batesville, AR talk about how residents and early career MDs process that decision.

The number of pregnant women with laboratory evidence of Zika virus infection jumped by 189 during the week ending Aug. 11, with most of the increase coming in the U.S. territories, according to the Centers for Disease Control and Prevention.

The territories reported 170 new cases of Zika infection for that week, while the 50 states and the District of Columbia had 19 new cases in pregnant women. There have been 1,220 cases in pregnant women in the United States so far: 691 in the territories and 529 in the states and D.C. Among all Americans, there have been 10,295 cases of Zika: 8,035 in the territories and 2,260 in the states/D.C., the CDC reported.

The number of Zika-related poor outcomes did not change during the week ending Aug. 11. The number of liveborn infants born with birth defects stayed at 16 in the states/D.C. and 1 in the territories, and the number of pregnancy losses with birth defects held at 5 in the states/D.C. and 1 in the territories, the CDC said. State- or territorial-level data are not being reported to protect the privacy of affected women and children.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

Zika virus–related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

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The number of pregnant women with laboratory evidence of Zika virus infection jumped by 189 during the week ending Aug. 11, with most of the increase coming in the U.S. territories, according to the Centers for Disease Control and Prevention.

The territories reported 170 new cases of Zika infection for that week, while the 50 states and the District of Columbia had 19 new cases in pregnant women. There have been 1,220 cases in pregnant women in the United States so far: 691 in the territories and 529 in the states and D.C. Among all Americans, there have been 10,295 cases of Zika: 8,035 in the territories and 2,260 in the states/D.C., the CDC reported.

The number of Zika-related poor outcomes did not change during the week ending Aug. 11. The number of liveborn infants born with birth defects stayed at 16 in the states/D.C. and 1 in the territories, and the number of pregnancy losses with birth defects held at 5 in the states/D.C. and 1 in the territories, the CDC said. State- or territorial-level data are not being reported to protect the privacy of affected women and children.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

Zika virus–related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

[email protected]

The number of pregnant women with laboratory evidence of Zika virus infection jumped by 189 during the week ending Aug. 11, with most of the increase coming in the U.S. territories, according to the Centers for Disease Control and Prevention.

The territories reported 170 new cases of Zika infection for that week, while the 50 states and the District of Columbia had 19 new cases in pregnant women. There have been 1,220 cases in pregnant women in the United States so far: 691 in the territories and 529 in the states and D.C. Among all Americans, there have been 10,295 cases of Zika: 8,035 in the territories and 2,260 in the states/D.C., the CDC reported.

The number of Zika-related poor outcomes did not change during the week ending Aug. 11. The number of liveborn infants born with birth defects stayed at 16 in the states/D.C. and 1 in the territories, and the number of pregnancy losses with birth defects held at 5 in the states/D.C. and 1 in the territories, the CDC said. State- or territorial-level data are not being reported to protect the privacy of affected women and children.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

Zika virus–related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

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DURBAN, SOUTH AFRICA – Screening for anal cancer in HIV-infected men or women should not be part of routine clinical practice at this time, Andrew Grulich, MBBS, PhD, declared at the 21st International AIDS Conference.

Some experts recommend anal cytologic screening or high-resolution anoscopy for HIV-positive men and women, but it’s worth noting that strategy hasn’t been incorporated into any national practice guidelines.

Bruce Jancin/Frontline Medical News

“And for very good reason: When we have a condition with a prevalence that’s so high and a treatment with recurrence rates that are so high, I think we need to question our approach,” said Dr. Grulich, professor of medicine and head of the HIV epidemiology and prevention program at the University of New South Wales in Sydney, Australia.

Screening proponents point to the high incidence of anal cancer in persons with HIV infection. It’s the fourth most common cancer in HIV patients in the United States, behind the AIDS-defining cancers and lung cancer. Indeed, the anal cancer rate is 10-fold greater in HIV-positive women, heterosexual men, and injection drug users than in the HIV-negative general population, and 50-fold higher in HIV-positive gay and bisexual men. Screening proponents also draw an analogy between anal cancer screening and the screening and treatment of cervical intraepithelial neoplasia (CIN), which has been enormously successful in preventing cervical cancer. But Dr. Grulich said he believes the cervical cancer screening analogy is faulty.

Colposcopy has a mean 90% specificity for diagnosis of HPV-related high-grade squamous intraepithelial lesions (HSIL) or cervical cancer, while high-resolution anoscopy as a diagnostic test has a specificity as low as 37% in HIV-positive persons. The prevalence of HSIL is 30%-40% in anal samples from HIV-infected homosexual men, compared with 1%-2% in cervical samples from HIV-negative women.

The rate of progression from CIN-3 to cervical cancer in women in the general population is about 1 in 80 per year. In contrast, the rate of progression from anal intraepithelial neoplasia (AIN)-2 or AIN-3 to anal cancer in HIV-infected homosexual men is estimated at only 1 in 400-600 per year, probably because regression of anal lesions is quite common.

Moreover, while a single treatment of high-grade CIN is typically curative and entails little morbidity, destruction of AIN by means of heat, cold, or electricity has a 70% failure rate, carries substantial morbidity, and is not supported by any evidence that it actually reduces the incidence of anal cancer, he continued.

“We’re in a bit of a quandary regarding what to do about anal cancer prevention. We really need research in order to move this field forward,” Dr. Grulich said.

He added that it’s worth keeping an eye on two ongoing studies addressing key questions surrounding anal cancer in HIV-positive persons. The U.S. National Cancer Institute–funded randomized ANCHOR trial is examining ablative therapy versus watchful waiting in HIV-infected patients with anal HSIL lesions; however, results of this large study aren’t expected until 2022 or 2023. And Dr. Grulich heads the Study of the Prevention of Anal Cancer, aimed at identifying biomarkers that predict persistence of HSIL as a marker of anal cancer risk.

A study he would very much like to see funded is a randomized, placebo-controlled, adequately powered trial of the 9-valent HPV vaccine in HIV-infected gay or bisexual men over age 26. At the 2016 meeting of the Conference on Retroviruses and Opportunistic Infections (CROI), Timothy J. Wilkin, MD, of Cornell University, New York, presented the results of the phase III ACTG A5298 trial of the quadrivalent HPV vaccine in HIV-infected adults over age 26. The vaccine group had a 27% reduction in risk of persistent anal HPV compared with placebo, which wasn’t statistically significant because of the small study size. The 9-valent vaccine would prevent a broader range of oncogenic HPV types.

Dr. Grulich reported receiving research funding from CSL Australia, Gilead Sciences, Viiv, and Hologic.

[email protected]

DURBAN, SOUTH AFRICA – Screening for anal cancer in HIV-infected men or women should not be part of routine clinical practice at this time, Andrew Grulich, MBBS, PhD, declared at the 21st International AIDS Conference.

Some experts recommend anal cytologic screening or high-resolution anoscopy for HIV-positive men and women, but it’s worth noting that strategy hasn’t been incorporated into any national practice guidelines.

Bruce Jancin/Frontline Medical News

“And for very good reason: When we have a condition with a prevalence that’s so high and a treatment with recurrence rates that are so high, I think we need to question our approach,” said Dr. Grulich, professor of medicine and head of the HIV epidemiology and prevention program at the University of New South Wales in Sydney, Australia.

Screening proponents point to the high incidence of anal cancer in persons with HIV infection. It’s the fourth most common cancer in HIV patients in the United States, behind the AIDS-defining cancers and lung cancer. Indeed, the anal cancer rate is 10-fold greater in HIV-positive women, heterosexual men, and injection drug users than in the HIV-negative general population, and 50-fold higher in HIV-positive gay and bisexual men. Screening proponents also draw an analogy between anal cancer screening and the screening and treatment of cervical intraepithelial neoplasia (CIN), which has been enormously successful in preventing cervical cancer. But Dr. Grulich said he believes the cervical cancer screening analogy is faulty.

Colposcopy has a mean 90% specificity for diagnosis of HPV-related high-grade squamous intraepithelial lesions (HSIL) or cervical cancer, while high-resolution anoscopy as a diagnostic test has a specificity as low as 37% in HIV-positive persons. The prevalence of HSIL is 30%-40% in anal samples from HIV-infected homosexual men, compared with 1%-2% in cervical samples from HIV-negative women.

The rate of progression from CIN-3 to cervical cancer in women in the general population is about 1 in 80 per year. In contrast, the rate of progression from anal intraepithelial neoplasia (AIN)-2 or AIN-3 to anal cancer in HIV-infected homosexual men is estimated at only 1 in 400-600 per year, probably because regression of anal lesions is quite common.

Moreover, while a single treatment of high-grade CIN is typically curative and entails little morbidity, destruction of AIN by means of heat, cold, or electricity has a 70% failure rate, carries substantial morbidity, and is not supported by any evidence that it actually reduces the incidence of anal cancer, he continued.

“We’re in a bit of a quandary regarding what to do about anal cancer prevention. We really need research in order to move this field forward,” Dr. Grulich said.

He added that it’s worth keeping an eye on two ongoing studies addressing key questions surrounding anal cancer in HIV-positive persons. The U.S. National Cancer Institute–funded randomized ANCHOR trial is examining ablative therapy versus watchful waiting in HIV-infected patients with anal HSIL lesions; however, results of this large study aren’t expected until 2022 or 2023. And Dr. Grulich heads the Study of the Prevention of Anal Cancer, aimed at identifying biomarkers that predict persistence of HSIL as a marker of anal cancer risk.

A study he would very much like to see funded is a randomized, placebo-controlled, adequately powered trial of the 9-valent HPV vaccine in HIV-infected gay or bisexual men over age 26. At the 2016 meeting of the Conference on Retroviruses and Opportunistic Infections (CROI), Timothy J. Wilkin, MD, of Cornell University, New York, presented the results of the phase III ACTG A5298 trial of the quadrivalent HPV vaccine in HIV-infected adults over age 26. The vaccine group had a 27% reduction in risk of persistent anal HPV compared with placebo, which wasn’t statistically significant because of the small study size. The 9-valent vaccine would prevent a broader range of oncogenic HPV types.

Dr. Grulich reported receiving research funding from CSL Australia, Gilead Sciences, Viiv, and Hologic.

[email protected]

DURBAN, SOUTH AFRICA – Screening for anal cancer in HIV-infected men or women should not be part of routine clinical practice at this time, Andrew Grulich, MBBS, PhD, declared at the 21st International AIDS Conference.

Some experts recommend anal cytologic screening or high-resolution anoscopy for HIV-positive men and women, but it’s worth noting that strategy hasn’t been incorporated into any national practice guidelines.

Bruce Jancin/Frontline Medical News

“And for very good reason: When we have a condition with a prevalence that’s so high and a treatment with recurrence rates that are so high, I think we need to question our approach,” said Dr. Grulich, professor of medicine and head of the HIV epidemiology and prevention program at the University of New South Wales in Sydney, Australia.

Screening proponents point to the high incidence of anal cancer in persons with HIV infection. It’s the fourth most common cancer in HIV patients in the United States, behind the AIDS-defining cancers and lung cancer. Indeed, the anal cancer rate is 10-fold greater in HIV-positive women, heterosexual men, and injection drug users than in the HIV-negative general population, and 50-fold higher in HIV-positive gay and bisexual men. Screening proponents also draw an analogy between anal cancer screening and the screening and treatment of cervical intraepithelial neoplasia (CIN), which has been enormously successful in preventing cervical cancer. But Dr. Grulich said he believes the cervical cancer screening analogy is faulty.

Colposcopy has a mean 90% specificity for diagnosis of HPV-related high-grade squamous intraepithelial lesions (HSIL) or cervical cancer, while high-resolution anoscopy as a diagnostic test has a specificity as low as 37% in HIV-positive persons. The prevalence of HSIL is 30%-40% in anal samples from HIV-infected homosexual men, compared with 1%-2% in cervical samples from HIV-negative women.

The rate of progression from CIN-3 to cervical cancer in women in the general population is about 1 in 80 per year. In contrast, the rate of progression from anal intraepithelial neoplasia (AIN)-2 or AIN-3 to anal cancer in HIV-infected homosexual men is estimated at only 1 in 400-600 per year, probably because regression of anal lesions is quite common.

Moreover, while a single treatment of high-grade CIN is typically curative and entails little morbidity, destruction of AIN by means of heat, cold, or electricity has a 70% failure rate, carries substantial morbidity, and is not supported by any evidence that it actually reduces the incidence of anal cancer, he continued.

“We’re in a bit of a quandary regarding what to do about anal cancer prevention. We really need research in order to move this field forward,” Dr. Grulich said.

He added that it’s worth keeping an eye on two ongoing studies addressing key questions surrounding anal cancer in HIV-positive persons. The U.S. National Cancer Institute–funded randomized ANCHOR trial is examining ablative therapy versus watchful waiting in HIV-infected patients with anal HSIL lesions; however, results of this large study aren’t expected until 2022 or 2023. And Dr. Grulich heads the Study of the Prevention of Anal Cancer, aimed at identifying biomarkers that predict persistence of HSIL as a marker of anal cancer risk.

A study he would very much like to see funded is a randomized, placebo-controlled, adequately powered trial of the 9-valent HPV vaccine in HIV-infected gay or bisexual men over age 26. At the 2016 meeting of the Conference on Retroviruses and Opportunistic Infections (CROI), Timothy J. Wilkin, MD, of Cornell University, New York, presented the results of the phase III ACTG A5298 trial of the quadrivalent HPV vaccine in HIV-infected adults over age 26. The vaccine group had a 27% reduction in risk of persistent anal HPV compared with placebo, which wasn’t statistically significant because of the small study size. The 9-valent vaccine would prevent a broader range of oncogenic HPV types.

Dr. Grulich reported receiving research funding from CSL Australia, Gilead Sciences, Viiv, and Hologic.

[email protected]